Antioxidant Effects of N-Acetylcysteine Prevent Programmed Metabolic Disease in Mice.

Abstract

An adverse maternal in utero and lactation environment can program offspring for increased risk for metabolic disease. The aim of this study was to determine whether N-acetylcysteine (NAC), an anti-inflammatory antioxidant, attenuates programmed susceptibility to obesity and insulin resistance in offspring of mothers on a high-fat diet (HFD) during pregnancy. CD1 female mice were acutely fed a standard breeding chow or HFD. NAC was added to the drinking water (1 g/kg) of the treatment cohorts from embryonic day 0.5 until the end of lactation. NAC treatment normalized HFD-induced maternal weight gain and oxidative stress, improved the maternal lipidome, and prevented maternal leptin resistance. These favorable changes in the in utero environment normalized postnatal growth, decreased white adipose tissue (WAT) and hepatic fat, improved glucose and insulin tolerance and antioxidant capacity, reduced leptin and insulin, and increased adiponectin in HFD offspring. The lifelong metabolic improvements in the offspring were accompanied by reductions in proinflammatory gene expression in liver and WAT and increased thermogenic gene expression in brown adipose tissue. These results, for the first time, provide a mechanistic rationale for how NAC can prevent the onset of metabolic disease in the offspring of mothers who consume a typical Western HFD.

• Authors: Maureen J Charron, Lyda Williams, Yoshinori Seki, Xiu Quan Du, Bhagirath Chaurasia, Alan Saghatelian, Scott A Summers, Ellen B Katz, Patricia M Vuguin, Sandra E Reznik
• Journal: Diabetes (Diabetes) Vol. 69 Issue 8 Pg. 1650-1661 (08 2020) ISSN: 1939-327X [Electronic] United States
• PMID: 32444367 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by the American Diabetes Association.

Chemical References

• Antioxidants
• Acetylcysteine

Topics

• Acetylcysteine (therapeutic use)
• Adipose Tissue, Brown (drug effects, metabolism)
• Adipose Tissue, White (drug effects, metabolism)
• Adiposity (drug effects)
• Animals
• Antioxidants (metabolism)
• Body Temperature
• Calorimetry, Indirect
• Diet, High-Fat (adverse effects)
• Female
• Glucose Tolerance Test
• Inflammation (drug therapy, metabolism)
• Injections, Intraperitoneal
• Insulin Resistance
• Male
• Metabolic Diseases (drug therapy, metabolism)
• Mice
• Weight Gain (drug effects)